Calix[n]arene-based immunogens: A new non-proteic strategy for anti-cocaine vaccine

Neto, Leonardo da Silva; Maia, Angélica Faleiros da Silva; Godin, Adriana M.; Augusto, Paulo Sérgio de Almeida; Pereira, Raissa Lima Gonçalves; Caligiorne, Sordaini Maria; Alves, Rosemeire Brondi; Fernandes, Simone Odília Antunes; Cardoso, Valbert Nascimento; Goulart, Gisele Assis Castro; Martins, Felipe Terra; Neves, Maila de Castro Lourenço das; Garcia, Fernando Coutinho; Fátima, Ângelo de

doi:10.1016/j.jare.2021.09.003

Cited by 6 publications

(7 citation statements)

References 76 publications

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“…Various methodological strategies have been evaluated to induce a robust immune response against drugs such as cocaine. 17 , 19 , 21 , 29 , 35 , 49 , 62 , 63 From the generation or optimization of new haptens to the use of new adjuvants capable of simultaneously stimulating various immunological pathways, passing through the use of various carrier proteins and different types of spacer arms. 18 , 20 , 37 , 40 , 48 , 50 …”

Section: Discussionmentioning

confidence: 99%

“…The hypothesis of the importance of the carrier protein as one of the structural elements of a conjugate vaccine that, when optimized, increases the immunogenic properties of a conjugate vaccine, is supported by evidence related to the synthesis of the so-called second or third-generation anti-cocaine vaccines. 17 , 19 , 21 , 29 , 35 , 49 , 62 , 63 In the search for highly immunogenic proteins, the dAd5GNE and dAd5GNC vaccines were developed. 21 , 29 , 62 , 73 To these vaccines, cocaine analogs called GNE and GNC were covalently coupled to the capsid proteins of adenoviral vectors (dAd) as carrier proteins.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, a new generation of cocaine vaccines called self-adjuvating cocaine vaccines have recently been developed, 17 , 19 , 35 , 49 , 63 in which nano scaffolds or nanoparticle platforms (flagellin, KFE8 peptide, PDD dendrimers, and calix[n]arene) were designed that could increase the surface-volume ratio to increase antigen presentation. optimize hapten coupling, improve hapten spatial organization, and simultaneously show adjuvant activity.…”

Section: Discussionmentioning

confidence: 99%

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COT-TT vaccine attenuates cocaine-seeking and cocaine-conditioned place preference in rats

Barbosa-Méndez,

Matus-Ortega,

Hernandez-Miramontes

et al. 2024

Human Vaccines & Immunotherapeutics

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Vaccination active, promising alternative immunological strategy to treat of CUD. Various models of cocaine vaccines have been evaluated in animals and humans with relative success. In this sense, it is necessary to improve or optimize the cocaine vaccines already evaluated. Our laboratory previously reported the efficacy of the tetanus toxoid-conjugated morphine vaccine (M 6 -TT). The M 6 -TT vaccine can generate high titers of antibodies and reduce heroin-induced behavioral effects in rodents. So, it would be plausible to assume that if we modify the M 6 -TT vaccine by changing the hapten and maintaining the rest of the structural elements of the vaccine, we will maintain the properties of the M 6 -TT vaccine (high antibody titers). The objective of this study was to determine whether the antibodies generated by a tetanus toxoid-conjugated cocaine vaccine (COC-TT) can recognize and capture cocaine and decrease the cocaine-induced reinforcing effects. Male Wistar rats were immunized with the COC-TT. A solid-phase antibody-capture ELISA was used to monitor antibody titer responses after each booster dose in vaccinated animals. The study used cocaine self-administration and place-preference testing to evaluate the cocaine-reinforcing effects. The COC-TT vaccine could generate high levels of anti-cocaine antibodies. The antibodies reduced the cocaine self-administration and cocaine place preference. In addition, they decreased the cocaine-induced Fos protein expression. These findings suggest that the COC-TT vaccine generates a robust immunogenic response capable of reducing the reinforcing effects of cocaine, which supports its possible future use in clinical trials in patients with CUD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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COT-TT vaccine attenuates cocaine-seeking and cocaine-conditioned place preference in rats

Barbosa-Méndez,

Matus-Ortega,

Hernandez-Miramontes

et al. 2024

Human Vaccines & Immunotherapeutics

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“…More recently, two innovative anti-cocaine immunogens based on calix[n]arene structures, designated as V4N2 and V8N2, promoted the production of cocaine antibodies and modulated the biodistribution of cocaine. At present, both V4N2 and V8N2 hold promise as potential candidates for the creation of immunogenic agents aimed at addressing cocaine use disorder [ 96 ]. However, more clinical trials are still needed to develop high-titer cocaine haptens and safe anti-cocaine vaccines.…”

Section: Recent Progress In Anti-drug Vaccine Researchmentioning

confidence: 99%

Vaccines to Treat Substance Use Disorders: Current Status and Future Directions

Lu,

Li,

Zheng

et al. 2024

Pharmaceutics

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Addiction, particularly in relation to psychostimulants and opioids, persists as a global health crisis with profound social and economic ramifications. Traditional interventions, including medications and behavioral therapies, often encounter limited success due to the chronic and relapsing nature of addictive disorders. Consequently, there is significant interest in the development of innovative therapeutics to counteract the effects of abused substances. In recent years, vaccines have emerged as a novel and promising strategy to tackle addiction. Anti-drug vaccines are designed to stimulate the immune system to produce antibodies that bind to addictive compounds, such as nicotine, cocaine, morphine, methamphetamine, and heroin. These antibodies effectively neutralize the target molecules, preventing them from reaching the brain and eliciting their rewarding effects. By obstructing the rewarding sensations associated with substance use, vaccines aim to reduce cravings and the motivation to engage in drug use. Although anti-drug vaccines hold significant potential, challenges remain in their development and implementation. The reversibility of vaccination and the potential for combining vaccines with other addiction treatments offer promise for improving addiction outcomes. This review provides an overview of anti-drug vaccines, their mechanisms of action, and their potential impact on treatment for substance use disorders. Furthermore, this review summarizes recent advancements in vaccine development for each specific drug, offering insights for the development of more effective and personalized treatments capable of addressing the distinct challenges posed by various abused substances.

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“…More recently, calix[n]arene-based vaccines (V4N2 and V8N2; Table 1) comprised of the cocaine hapten GNE tethered to calix[n]arene elicited strong titers of cocaine antibodies that modified the biodistribution of a cocaine radiolabeled analogue, decreasing cocaine-induced behavior in mice. 47 Calix[n]arene is a cyclic oligomer (macrocycle) based on methylene-linked phenols and allows for the multipresentation of GNE to antigenpresenting cells (similar to protein-based carriers), avoiding the need for sterilization and a cold supply chain associated with protein-based vaccine pathways. This synthetic delivery/ adjuvant system negated the use of protein carriers in its vaccine design and will be instrumental in the development of anti-drug vaccines moving forward.…”

Section: Pre-clinical Advances Inmentioning

confidence: 99%

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

Stephenson

Tóth

2023

J. Med. Chem.

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Cocaine is one of the oldest and most widely used illicit drugs in the world and is responsible for major worldwide medical and social problems. Drug addiction is a disease state where the body relies on a substance for normal functioning and develops a physical dependence leading to compulsive and repetitive use despite negative consequences to the user's health, mental state, or social life. The primary driver for the development of anti-cocaine vaccines has been the failure to develop effective pharmacological treatments to combat cocaine dependence. Despite several decades of research, no approved pharmacological treatments for cocaine dependence are available to assist addicts to overcome cocaine withdrawal or to prevent drug relapse. This Perspective highlights the challenges associated with anti-cocaine vaccines, including the current state of anti-cocaine vaccines and catalytic antibody research to aid in the fight against cocaine addiction.

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Calix[n]arene-based immunogens: A new non-proteic strategy for anti-cocaine vaccine

Cited by 6 publications

References 76 publications

COT-TT vaccine attenuates cocaine-seeking and cocaine-conditioned place preference in rats

COT-TT vaccine attenuates cocaine-seeking and cocaine-conditioned place preference in rats

Vaccines to Treat Substance Use Disorders: Current Status and Future Directions

Anti-cocaine Vaccine Development: Where Are We Now and Where Are We Going?

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